Peroxynitrite aggravates myocardial reperfusion injury in the isolated perfused rat heart.
OBJECTIVE
This study examined the effects of peroxynitrite (ONOO-) on cardiac function and cellular injury following ischemia (30 min) and reperfusion (60 min) in isolated perfused rat hearts.


METHODS
3-Morpholinosydnonimine (SIN-1, 0.1 mM), an ONOO- donor, was administered alone or combined with superoxide dismutase (SOD, 300 U/ml) or glutathione (GSH, 1 mM) at the time of reperfusion.


RESULTS
Administration of SIN-1 alone significantly aggravated post-ischemic myocardial injury characterized by depressed cardiac function recovery (p < 0.05 vs. vehicle), increased lactic dehydrogenase (LDH) and creatine kinase (CK) release (p < 0.01 vs. vehicle), and enlarged necrotic size (p < 0.01 vs. vehicle). The co-administration of either SOD to decrease the formation of ONOO-, or GSH to increase the detoxification of ONOO-, completely blocked the detrimental effects of SIN-1 and exerted significant cardioprotective effects against reperfusion injury.


CONCLUSIONS
These results suggest that ONOO- may play a significant role in postischemic myocardial injury.
Ma
X L
XL
Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107-5004, USA.
Lopez
B L
BL
Liu
G L
GL
Christopher
T A
TA
Ischiropoulos
H
H
D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000209:etiology*; D009206:Myocardium / Q000201:enzymology; D009566:Nitrates / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D009566:Nitrates; D014665:Vasodilator Agents; C039642:peroxynitric acid; C002385:linsidomine; D008981:Molsidomine; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D005978:Glutathione